Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto, Brazil.
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto, Brazil.
Food Chem Toxicol. 2019 Oct;132:110694. doi: 10.1016/j.fct.2019.110694. Epub 2019 Jul 22.
The present study evaluates the effects of low-level long-term exposure to bisphenol A (BPA) and bisphenol S (BPS) on serum biochemical markers, glucose homeostasis, mitochondrial energy metabolism, biogenesis and dynamics, and redox status in livers of Wistar rats. While only the exposure to BPS induces a significant body mass gain after 21 weeks, both compounds alter serum lipid levels and lead to the development of glucose intolerance. Regarding mitochondrial metabolism, both bisphenols augment the electron entry by complex II relative to complex I in the mitochondrial respiratory chain (MRC), and reduce mitochondrial content; BPA reduces OXPHOS capacity and uncouples respiration (relative to maximal capacity of MRC) but promotes a significant increase in fatty acid oxidation. Either exposure to BPA or BPS leads to an increase in mitochondrial-derived reactive oxygen species, mainly at complex I. Additionally, BPA and BPS significantly upregulate the expression levels of dynamin-related protein 1 related to mitochondrial fission, while BPA downregulates the expression of proliferator-activated receptor gamma coactivator 1 alpha, a master regulator of mitochondrial biogenesis. In summary, our data shows that exposure to both compounds alters metabolic homeostasis and mitochondrial energy metabolism, providing new mechanisms by which BPA and BPS impair the mitochondrial metabolism.
本研究评估了低水平长期暴露于双酚 A（BPA）和双酚 S（BPS）对 Wistar 大鼠血清生化标志物、葡萄糖稳态、线粒体能量代谢、生物发生和动力学以及肝脏氧化还原状态的影响。虽然仅暴露于 BPS 会在 21 周后导致显著的体重增加，但这两种化合物都会改变血清脂质水平并导致葡萄糖耐量受损。关于线粒体代谢，这两种双酚类化合物都增加了线粒体呼吸链（MRC）中相对于复合物 I 的复合物 II 的电子进入，并且减少了线粒体含量；BPA 降低了 OXPHOS 能力并使呼吸解偶联（相对于 MRC 的最大能力），但促进了脂肪酸氧化的显著增加。暴露于 BPA 或 BPS 都会导致线粒体来源的活性氧增加，主要发生在复合物 I。此外，BPA 和 BPS 显著上调了与线粒体分裂相关的 dynamin 相关蛋白 1 的表达水平，而 BPA 下调了线粒体生物发生的主要调节因子过氧化物酶体增殖物激活受体γ共激活因子 1α的表达水平。总之，我们的数据表明，暴露于这两种化合物会改变代谢稳态和线粒体能量代谢，为 BPA 和 BPS 损害线粒体代谢提供了新的机制。
